InVivo Therapeutics (NASDAQ:NVIV) Investor …...2019/11/18 · InVivo Therapeutics (NASDAQ:NVIV) 2...

1InVivo Therapeutics (NASDAQ:NVIV)

InVivo Therapeutics (NASDAQ:NVIV)Investor Presentation

Developing Innovative Products for Spinal Cord Injury

November 2019


Forward-Looking Statements

Any statements in this presentation about future expectations, plans and prospects for InVivo Therapeutics HoldingsCorp. (the “Company”), including statements regarding the safety and effectiveness of the Neuro-Spinal Scaffold™, theanticipated value of the second pivotal study, the expected timing for enrollment and completion of the secondpivotal study, the expected timing for the Company’s data read-outs, medical publications and presentations, theestablishment of the Neuro-Spinal Scaffold™ as the first and foundation of spinal cord injury (“SCI”) treatments, thestatus of the clinical program, and other statements containing the words “believes,” “anticipates,” “targets,” “plans,”“expects,” “estimates,” and similar expressions, constitute forward-looking statements within the meaning of ThePrivate Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by suchforward-looking statements as a result of various important factors, including risks and uncertainties relating to theCompany’s ability to raise capital and to initiate, conduct and complete clinical trials; the Company’s ability to submitan HDE application and receive regulatory approval for the Neuro-Spinal Scaffold; the impact of achieving the ObjectivePerformance Criterion on the U.S. Food and Drug Administration (the “FDA”) approval process; the Company’s abilityto commercialize its products; the Company’s ability to develop, market and sell products based on its technology;the expected benefits and efficacy of the Company’s products and technology in connection with the treatment ofspinal cord injuries; the availability of substantial additional funding for the Company to continue its operations andto conduct research and development, clinical studies and future product commercialization and other factorsdiscussed in the “Risk Factors” section of our most recent quarterly report on Form 10-Q filed with the Securities andExchange Commission (the “SEC”) and in the Company’s other filings from time to time with the SEC. In addition, theforward-looking statements included in this presentation represent the Company’s views as of the date hereof andshould not be relied upon as representing the Company’s views as of any date subsequent to the date hereof. TheCompany anticipates that subsequent events and developments will cause the Company’s views to change. However,while the Company may elect to update these forward-looking statements at some point in the future, the Companyspecifically disclaims any obligation to do so.


InVivo Therapeutics Executive Summary

• Developing the Investigational Neuro-Spinal Scaffold™ for Acute Spinal Cord Injury (SCI) and actively searching for synergistic pipeline expansion opportunities– No effective treatments available for SCI and no direct competitive products in clinical development

– Completed pivotal probable benefit study: INSPIRE 1.0; Second active pivotal study: INSPIRE 2.0

• INSPIRE 1.0: Key Observations– Demonstrated surgical feasibility of acute Neuro-Spinal Scaffold™ implantation

– Reported AIS conversion rate that exceeds published natural history rates and Objective Performance Criterion

– Observed delayed conversions at 12 and 24 months

– Applied learnings from INSPIRE 1.0 to mitigate risk in INSPIRE 2.0

• INSPIRE 2.0: Active pivotal study of the Neuro-Spinal Scaffold™– Encouraging data from single-arm INSPIRE 1.0 study supports follow-on study

– Two-arm, 20-patient (10 subjects in each study arm) randomized, controlled trial designed to provide clinical data that will supplement the existing INSPIRE 1.0 clinical results

– Estimated that from study initiation, enrollment will take place over approximately 18 months at an estimated 20 sites, with the full study completing in two years

– As of November 1, 2019, five patients have been enrolled and 14 sites are active

• Desire to expand pipeline beyond the Neuro-Spinal Scaffold with technologies that align with the company’s core competencies– Announced Joint Research Collaboration with Q Therapeutics, Inc. in October 2018: Aims to evaluate the preclinical

safety and feasibility of the Neuro-Spinal Scaffold™ with stem cells

• $8.1 M in cash and cash equivalents as of 9/30/19; no debt


Spinal Cord Injury: An Unmet Clinical Need with No Effective Treatments

• Unserved patient population with no options

– Approximately 17,000 new cases of acute SCI per year in US1

– Patients affected by loss of motor, sensory and autonomic (bowel, bladder and sexual) function

– Only small percentage of patients ever regain function3

– Approximately 285,000 currently live with chronic SCI in US2

▪ Chronic SCI: >6 months after injury

• Direct cost of spinal cord injury

– Cost of care for the first year post-SCI: $350K - $1.0M+2

– Net present value of the cost for a quadriplegic injured at 25 for life: $4.8M+2

1. Neurosurgeon & Payer Interviews; NSCISC 2017 Annual Report; Selvarajah et al., J. Neurotrauma (2014); Outside Consultant Analysis. 2. National Spinal Cord Injury Statistical Center, Facts and Figures at a Glance. Birmingham, AL: University of Alabama at Birmingham, 2017.3. Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: spontaneous recovery after spinal cord injury and statistical power

needed for therapeutic clinical trials. Spinal cord (2007).

We seek to establish the Neuro-Spinal Scaffold as the foundation of the standard of care for acute SCI


Acute Management of Spinal Cord Injury

• Currently available acute management of SCI:

– Non-surgical management:

▪ traction and bedrest to prevent additional trauma

– Surgical Management:

▪ Bony decompression and spinal column alignment and stabilization

▪ Minimizes secondary injury and provides support to the spine

• Standard of care:

– Early decompressive surgery within 24-48 hours post-injury

– Attempts to remove ongoing spinal cord compression

Despite significant advances in surgical repair to the spinal column over recent decades, modern day acute management of SCI does not address repair of the spinal cord


Progression of Acute SCI to Post-Traumatic Cavityin Contusion Injuries

Poster D8-06; National Neurotrauma Society 2015 Symposium; Santa Fe, NM.

Spinal CordInjury

Hemorrhage&

Spinal Cord Swelling

Reduced Blood Flow

&Ischemic Necrosis

CavityDevelopment

&White Matter

Reduction

Chronic injury and mature

cavity formation

Time

White matter

Highly vascularized gray matter

Acute hemorrhage & necrosis Mature cavityLiquefactive necrosis

Normal 2 hours after SCI 24 hours after SCI 12 weeks after SCI

Histology from rat contusion model of SCI


The Neuro-Spinal Scaffold™:

InVivo’s Approach for Acute SCI


The Neuro-Spinal Scaffold™

• Proprietary, highly porous biopolymer Neuro-Spinal Scaffold– PLGA is the biodegradable skeleton along which cells can grow– Poly-L-Lysine promotes cellular adhesion

• Scaffold is surgically implanted lengthwise into cavity created by SCI

• Issued patents covering Neuro-Spinal Scaffold licensed from MIT and Boston Children’s Hospital (expires 2027)

Company images


Neuro-Spinal Scaffold™ Mechanism of Action

• Preservation of white matter and reduction of cyst formation via appositional healing (i.e., spinal cord architecture)

• Neural regeneration through the formation of neuro-permissive remodeled tissue

• Remyelination of segmentally demyelinated white matter axons by Schwann cells

Remyelination with Schwann Cells after Neuro-Spinal Scaffold™ Implantation*

Schwann Cells restore signal transduction

Contusion Injury White MatterEpicenter

Schwann Cells aid neural regeneration

Central epicenter (a) and white matter (b)

*Rat Acute Spinal Cord Contusion Injury (at 12 weeks)


The Neuro-Spinal Scaffold™ Preserves Macroscopic Spinal Cord Architecture

Control Scaffold

*P<0.05

Rem

od

ele

d T

issu

e

Vo

lum

e (

mm

3)

Control Scaffold0.0

0.5

1.0

1.5

2.0 *

Cavit

y V

olu

me (

mm

3)

Control Scaffold0

2

4

6

*

Wh

ite M

att

er

Wid

th (

mm

)

Control Scaffold0.0

0.2

0.4

0.6 *Cyst Reduction White Matter Sparing Remodeled Tissue

Poster D8-06; National Neurotrauma Society 2015 Symposium; Santa Fe, NM.

Rat Acute Spinal Cord Contusion Injury (at 12 weeks)

Neuro-Spinal ScaffoldControl

Cyst

Neuro-Spinal

ScaffoldNeuro-Spinal

Scaffold

Neuro-Spinal

Scaffold


Neuro-Spinal Scaffold™ Promotes Neural Regeneration and Functional Recovery

Increased remodeled tissue

Slotkin JR et al., Biomaterials. (2017)

Neural regenerationMyelin basic protein stained

axons in remodeled tissue

Improved functional recovery

Primate Hemicordectomy Model (at 3 Months)

Neuro-Spinal

Scaffold

Hemicordectomy Model

*P<0.05


Neuro-Spinal Scaffold™

Clinical & Regulatory Development Plans


Humanitarian Device Exemption (HDE):A Lower Approval Threshold

*Excludes penetrating injuries such as gunshot or knife injuries

Benefit – Provides less burdensome regulatory process (lower approval threshold)– Demonstrate safety and probable benefit (rather than effectiveness)

21st

Century Cures Act

– InVivo’s initial Humanitarian Use Device population: thoracic and cervical SCI patients with complete paralysis (AIS A)*

– May allow InVivo to take advantage of the HDE pathway for patients with incomplete paralysis (AIS B and AIS C)*

– Would require applying for expanded HUD and conducting a separate study– As required by the Cures Act, the FDA published draft guidance that further

defines the criteria for establishing “probable benefit” in June 2018– We reviewed this against our current clinical plan and believe that our

plans remain appropriate and consistent with the draft guidance

Market Advantage

– Eligible to be sold for profit for adult and pediatric patients (defined as patients age 21 and under)

– Device is intended for the treatment of a condition that occurs in and is labeled for use in pediatric patients or in a pediatric subpopulation


INSPIRE 1.0Foundational Study

• Trial Design:– 20-patient, single arm trial, evaluating whether

the Scaffold is safe and demonstrates probable benefit for the treatment of AIS A T2-T12/L1 spinal cord injury (within 96 hrs of injury)

• Primary Endpoint: – Improvement in ASIA Impairment Scale (AIS)

grade from baseline at 6 months

• Trial Success Criterion (Objective Performance Criterion): – At least 25% of subjects convert from complete

paraplegia (AIS A) to partial paralysis by 6 months

American Spinal Injury Association Impairment Scale (AIS)

Grade Description (Abridged)

AComplete – No motor or sensory function

preserved in sacral segments (S4-5)

BSensory Incomplete – Sensory but not

motor function preserved below level of injury and includes sacral segments

C

Motor Incomplete – Motor function preserved below level of injury; voluntary

anal contraction OR sparing of motor function 3 levels below injury

DMotor Incomplete – Similar to AIS C but with at least half of key muscles below

injury functioning against gravity

E Normal


INSPIRE 1.0: AIS Conversion Rate vs. Objective Performance Criterion for Evaluable Patients at 6 Months (Primary Endpoint)

Published historical benchmarks for AIS conversion rates were used to establish the OPC

15.6% 15.5%

36.8%

43.8%

0%

10%

20%

30%

40%

50%

EMSCI(n=256, 6 months)

Model Systems(n=194, 12 months)

INSPIREAll Patients

(n=19, 6 months)

INSPIREEvaluable Patients(n=16, 6 months)

Complete (AIS A) Thoracic SCI AIS Conversions

1 Zariffa et al., Spinal Cord (2011); European Multicenter Study about Spinal Cord Injury (EMSCI)2 Lee et al., J. Spinal Cord Med (2014); Spinal Cord Injury Model System (US)3 Approval is not guaranteed if the OPC is met and HDE approval may still be obtained if OPC is not met if probable benefit outweighs the risk.

= 7/16* evaluable patients have converted at 6 months

OPC = study success3

(25%)

1 2

*Two patients were lost to follow up after the 6 month visit

*Three additional subjects died within two weeks of implantation


• Study design– Subjects randomized to two treatment arms – Scaffold Arm and Comparator

Arm (standard of care spine stabilization without dural opening/myelotomy)– Single blind – subjects and assessors blinded to treatment assignment– Plan to enroll 20 subjects (10 in each treatment arm) across US clinical sites

• Clinical study in support of an HDE application– Primary endpoint: Improvement in ASIA Impairment Scale (AIS) grade by 6

months – Assessments at hospital discharge, 3, 6 (primary endpoint), 12 and 24 months

• Definition of Success: Proportion of subjects with AIS grade improvement assessed at 6 month follow-up timepoint

% Scaffold Arm subjects w/AIS grade improvement

% Comparator Arm subjects w/AIS grade improvement

_ ≥ 20% SUCCESS

INSPIRE 2.0:A Clear Path Forward


InVivo Anticipated Clinical Milestones

Clinical Milestones (Inspire 1.0 and 2.0)

2019

Q2• Presentation of 12 month data (AANS) (Inspire 1.0)• First patient enrolled (Inspire 2.0)

Q3 • Submission for publication of six month data (Inspire 1.0)

Q4• Joint submission for publication of 12 and 24 month data (Inspire 1.0)• Presentation of 24 month data (CNS) (Inspire 1.0)• Submission of pathology publication (Inspire 1.0)

2020

Q1 • Acceptance of publication of six month data (Inspire 1.0)

Q2• Acceptance of joint publication of 12 and 24 month data (Inspire 1.0)• Presentation of 24 month data (AANS) (Inspire 1.0)


The Neuro-Spinal Scaffold:

Commercial Opportunity


INSPIRE Clinical Population Patient Distribution

17,000 Acute SCIs per year

13,200 Aged 16-70

2,200 Thoracic A

Injury Grade

1,500 Thoracic A Non-

penetrating injuries without

transection

INSPIRE Study Clinical Population

(1.0 and 2.0)

3,200 Thoracic

8,000Cervical

2,000Lumbar

2,900 Cervical A

Injury Grade

Age

SCI Level

Injury Grade: A

Exclusion of penetrating and complete transection injuries Source: Neurosurgeon & Payer Interviews; NSCISC 2017 Annual

Report; Selvarajah et al., J. Neurotrauma (2014); Outside Consultant Analysis.


InVivo Therapeutics Executive Summary

• Developing the Investigational Neuro-Spinal Scaffold™ for Acute Spinal Cord Injury (SCI) and actively searching for synergistic pipeline expansion opportunities– No effective treatments available for SCI and no direct competitive products in clinical development

– Completed pivotal probable benefit study: INSPIRE 1.0; Second active pivotal study: INSPIRE 2.0

• INSPIRE 1.0: Key Observations– Demonstrated surgical feasibility of acute Neuro-Spinal Scaffold™ implantation

– Reported AIS conversion rate that exceeds published natural history rates and Objective Performance Criterion

– Observed delayed conversions at 12 and 24 months

– Applied learnings from INSPIRE 1.0 to mitigate risk in INSPIRE 2.0

• INSPIRE 2.0: Active pivotal study of the Neuro-Spinal Scaffold™– Encouraging data from single-arm INSPIRE 1.0 study supports follow-on study

– Two-arm, 20-patient (10 subjects in each study arm) randomized, controlled trial designed to provide clinical data that will supplement the existing INSPIRE 1.0 clinical results

– Estimated that from study initiation, enrollment will take place over approximately 18 months at an estimated 20 sites, with the full study completing in two years

– As of November 1, 2019, five patients have been enrolled and 14 sites are active

• Desire to expand pipeline beyond the Neuro-Spinal Scaffold with technologies that align with the company’s core competencies– Announced Joint Research Collaboration with Q Therapeutics, Inc. in October 2018: Aims to evaluate the preclinical

safety and feasibility of the Neuro-Spinal Scaffold™ with stem cells

• $8.1 M in cash and cash equivalents as of 9/30/19; no debt

InVivo Therapeutics (NASDAQ:NVIV) Investor …...2019/11/18 · InVivo Therapeutics (NASDAQ:NVIV) 2...

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Transcript of InVivo Therapeutics (NASDAQ:NVIV) Investor …...2019/11/18 · InVivo Therapeutics (NASDAQ:NVIV) 2...